1. Field of the Invention
The present invention relates to novel piperine derivatives and uses thereof.
2. Background of Technique
As abdominal obesity increases in modern people with the change in lifestyles, occurrence of metabolic syndromes including diabetes, hypertension, dyslipidemia, insulin resistance, etc. is increasing rapidly. These diseases increase the risk of incidence one another and are commonly related to the cause of metabolic changes, such as aging, stress and suppressed immune system. Obesity is considered unattractive and causes such chronic diseases as fatty liver, hypertension, diabetes, cardiovascular diseases, or the like. According to the 2007 Korea National Health and Nutrition Examination Survey recently reported by the Ministry of Health & Welfare, 31.7% of Korean adults turned out to be obese, meaning that 3 out of 10 Korean adults are exposed to obesity-related complications. The increase in overweight and obese population leads to increased prevalence of chronic diseases. The number of diabetic patients in Korea is expected to increase from 3,000,000 in 2007 to 5,450,000 in 2030, meaning that 10% of Koreans will be diabetic patients. In 2005, deaths caused by diabetes in Korea were 35.5 per 100,000 people, 3-7 times more than those of Japan (5.9), England (7.5) or Germany (16.6). According to the Korea Institute for Health and Social Affairs, the socioeconomic loss caused by obesity and obesity-related complications in 2006 is estimated at 2.1 trillion won including medical cost and indirect cost such as loss of earning. Thus, in 2010, the Korean government has decided to reduce the obesity rate down to 20% in adults and to 15% in youth, and is exploring ways to accurately define and diagnose obesity and metabolic diseases.
At present, 1.7 billion people amounting to about 25% of the world population are overweight (BMI>25) and more than 300 million people including 120 million in the US, Europe and Japan are classified as obese (BMI>30). Among the OECD countries, the US has the highest obesity rate of 31% of population, followed by Mexico (24%), England (23%), Greece (22%), Australia (22%), New Zealand (21%), Hungary (19%), Canada (14%), Spain (13%), Ireland (13%), Germany (13%), Portugal (13%), Finland (13%), Turkey (12%) and Belgium (12%). The number of obese people in China is 70 million and the body weight control-related market is expanding, estimated at about 10 billion yuan. Childhood obesity is also increasing rapidly worldwide, with 1 in 5 children being obese. As such, childhood obesity is becoming a serious social issue. Since childhood obesity is the main cause of the life style diseases including diabetes, hypertension, stroke, etc. with increased blood cholesterol and triglyceride level, 80% or more of obese children are likely to become obese adults. Further, since increased fat stimulates secretion of sex hormones and induces early adolescence, childhood obesity may cause growth problems. Also, it negatively affects blood circulation and nourishment.
Obesity drugs that are marketed inside and outside Korea include ‘Xenical’ (Roche Korea) with orlistat as main ingredient and approved by the FDA, ‘Reductil’ (Ilsung Pharmaceuticals) with sibutramine as main ingredient, ‘Exolise’ (Guju Pharma) with green tea catechol as main ingredient, or the like. Xenical, which reduces absorption of fat by inhibiting lipase, has the gastrointestinal-related side effects such as steatorrhea, gas generation and reduced absorption of oil-soluble vitamins. Reductil, which increases serotonin and noradrenaline levels in the sympathetic nervous system, has side effects such as headache, dry mouth, loss of appetite, insomnia, constipation, etc. Besides, a large number of anti-obesity drugs have been withdrawn from the market due to severe side effects. For example, aminophylline is reported to have various side effects in the nervous, circulatory and digestive systems despite its excellent effect of reducing body fat. Also, fenfluramine, dexfenfluramine, topiramate, ephedrine, etc. have been banned from being marketed as obesity drugs. As the synthetic drugs show limitations in side effects and in overcoming chronic diseases, foods and drugs derived from natural sources are drawing attentions.
Piperine is a compound found in long pepper, black pepper, cubeb, or dill, and its structural formula is C17H19NO3. It has been so far reported that piperine has biological activities such as an antioxidant effect, an anti-mutagenic effect, and an anti-cancer effect, and serves to improve bioavailability of drugs such as resveratrol. The treatment of endothelial cells with piperine led to effective immune responses, such as increasing adhesion of neutrophils and leukocytes and suppressing migration of the p65 subunit of NK-kB from the cytoplasm to the nucleus. For Swiss albino mice, as a result of comparison between a group administered with of benzo[α]pyrene, which is carcinogen causing lung cancer, in an amount of 50 mg/kg body weight twice a week for 16 weeks and a group administered with piperine in an amount of 100 mg/kg body weight once a day for 4 weeks before administration of benzo[α]pyrene, the group pre-treated with piperine showed significantly high values of antioxidant indexes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), vitamin E, vitamin C, or the like in the tissues. Thus, piperine was proven to have an antioxidant effect. Accordingly, piperine has been commercially used for products of various dietary supplements in a complex form, together with other plant extracts and phytochemicals, and has been on the market for the purpose of improving general health functions including an antioxidant function.
Throughout the specification, a number of publications and patent documents are referred to and cited. The disclosure of the cited publications and patent documents is incorporated herein by reference in its entirety to more clearly describe the state of the related art and the present disclosure.